U.S. patent application number 12/877233 was filed with the patent office on 2012-03-08 for lubricious coatings for medical devices.
Invention is credited to Simon Jon Onis, Alan Rhodes, Shivpal S. Sandhu.
Application Number | 20120059111 12/877233 |
Document ID | / |
Family ID | 44774077 |
Filed Date | 2012-03-08 |
United States Patent
Application |
20120059111 |
Kind Code |
A1 |
Sandhu; Shivpal S. ; et
al. |
March 8, 2012 |
LUBRICIOUS COATINGS FOR MEDICAL DEVICES
Abstract
Substrates may be coated with copolymers of N-vinyl
pyrrolidinone and aryl ketones. Processes are described for making
the copolymers at high molecular weight with the ketones randomly
dispersed on the copolymer.
Inventors: |
Sandhu; Shivpal S.;
(Buckinghamshire, GB) ; Rhodes; Alan; (Reading,
GB) ; Onis; Simon Jon; (Reading, GB) |
Family ID: |
44774077 |
Appl. No.: |
12/877233 |
Filed: |
September 8, 2010 |
Current U.S.
Class: |
524/548 ;
427/2.1; 427/2.24; 427/2.3; 525/203; 526/263 |
Current CPC
Class: |
A61L 2400/10 20130101;
A61N 1/056 20130101; A61L 31/10 20130101; A61L 29/085 20130101;
A61L 27/34 20130101; C09D 133/062 20130101 |
Class at
Publication: |
524/548 ;
525/203; 427/2.1; 427/2.24; 427/2.3; 526/263 |
International
Class: |
C08L 39/06 20060101
C08L039/06; C08F 226/10 20060101 C08F226/10; B05D 3/06 20060101
B05D003/06 |
Claims
1. A coating on a medical device comprising a hydrophilic layer
comprising copolymers covalently crosslinked by photoinitiation of
diaryl ketones pendant on the copolymers, with the copolymers,
before photoinitiation, being polymerized from a plurality of
monomers comprising N-vinyl pyrrolidinone and diaryl ketone vinyl
monomer, having a weight average molecular weight of more than
about 100,000, at least about 60% by weight N-vinyl pyrrolidinone,
no more than about 5% by weight of diaryl ketone monomer that
provides the pendant diaryl ketones, and a random distribution of
the diaryl ketones.
2. The coating of claim 1, wherein the coating has a friction
coefficient of no more than about 0.2.
3. The coating of claim 1 wherein the diaryl ketone is
benzophenone.
4. The coating of claim 1 wherein the diaryl ketone monomer
comprises a methacrylate group or an acrylate group.
5. The coating of claim 1 wherein the diaryl ketone of the
copolymers is selected from the group consisting of
2-hydroxybenzophenone, 3-hydroxybenzophenone,
4-hydroxybenzophenone, 2,2'-dihydroxybenzophenone,
2,4-dihydroxybenzophenone, 3,4-dihydroxybenzophenone,
4,4'-dihydroxybenzophenone, 2,3,4-trihydroxybenzophenone,
2,4,4'-trihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone,
2-aminobenzophenone, 3-aminobenzophenone, 4-aminobenzophenone,
3,4-diaminobenzophenone, 4,4'-diamonibenzophenone,
4-(bromomethyl)benzophenone, 2-benzoylbenzoic acid,
3-benzoylbenzoic acid, 4-benzoylbenzoic acid, 4-benzoylbenzoyl
chloride, 4-isocyanatobenzophenone,
benzophenone-3,3',4,4'-tetracarboxylic dianhydride,
3-bromo-2',5-dichloro-2-hydroxybenzophenone,
2-hydroxy-2',3,5-trichlorobenzophenone,
3-bromo-5-chloro-2-hydroxybenzophenone,
5-bromo-2'-chloro-2-hydroxybenzophenone,
4'-chloro-5-fluoro-2-hydroxybenzophenone,
2',5-dichloro-2-hydroxybenzophenone, 5-bromo-2-hydroxybenzophenone,
4-fluoro-4'-hydroxybenzophenone, 2-amino-4'-bromobenzophenone,
2-amino-5-chlorobenzophenone, 4-amino-3-nitrobenzophenone,
2'-chloro-2-hydroxy-4-methylbenzophenone,
2'-chloro-2-hydroxy-5-methylbenzophenone,
2-hydroxy-5-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone,
2-amino-4-methylbenzophenone, benzoin, 4,4'-dimethoxybenzoin,
4-chlorobenzoin, benzyl 4-hydroxyphenyl ketone, benzyl
2,4-dihydroxyphenyl ketone,
2-phenyl-2',4',6'-trihydroxyacetophenone.
6. The coating of claim 1 wherein the diaryl ketone monomer
comprises a polymerizable group selected from the group consisting
of acrylate groups, methacrylate groups, and methylmethacrylate
groups.
7. The coating of claim 1 wherein the plurality of monomers further
comprises one or more monomers selected from the group consisting
of poly(ethylene glycol) methacrylate, poly(propylene glycol)
methacrylate, poly(ethylene glycol) methyl ether methacrylate,
poly(ethylene glycol) ethyl ether methacrylate, 3-trimethoxysilyl
propyl methacrylate, vinyl sulfonic acid (sodium salt), ammonium
sulfatoethyl methacrylate, 2-acryloylamido-2-methylpropanesulfonic
acid monomer,
[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium
hydroxide (MEDSAH),
[3-(methacryloylamino)propyl]dimethyl-(3-sulfopropyl)ammonium
hydroxide (MPDSAH), 2-methacryloyloxyethyl phopshorylcholine (MPC),
acrylic acid (sodium salt), dimethylaminoethyl methacrylate,
2-hydroxyethyl methacrylate (HEMA), polyhexanide methacrylate and
chlorhexidine methacrylate.
8. The coating of claim 1 wherein the plurality of monomers further
comprises a monomer that comprises a polyethylene glycol pendant
group.
9. The coating of claim 1 wherein the plurality of monomers further
comprises a monomer that comprises a pendant group terminating in a
sulfonate group.
10. The coating of claim 1 wherein the plurality of monomers
further comprises a monomer that comprises a silyl pendant
group.
11. The coating of claim 1 wherein the plurality of monomers
further comprise a monomer that comprises a zwitterionic group.
12. The coating of claim 1 wherein the plurality of monomers
further comprise a monomer that comprises a hydroxyl group.
13. The coating of claim 1 wherein the copolymers, before
photoinitiation, consist essentially of the polymerization product
of the N-vinyl pyrrolidinone and the diaryl ketone monomer.
14. The coating of claim 1 wherein the medical device is selected
from the group consisting of a stent, a guidewire, a pacemaker
lead, a catheter, a medical balloon, a nasogastric feeding tube,
and an endotracheal tube.
15. An isolated set of polymers comprising copolymers polymerized
from monomers comprising N-vinyl pyrrolidinone monomer and a diaryl
ketone vinyl monomer, with the copolymers having a weight average
molecular weight of more than about 100,000, at least about 60% by
weight N-vinyl pyrrolidinone, no more than about 5% by weight
diaryl ketone monomer, and a random distribution of the diaryl
ketone in the copolymer.
16. A method of coating a medical device comprising exposing a
medical device to copolymers having a weight average molecular
weight of more than about 100,000, at least about 60% by weight
N-vinyl pyrrolidinone, diaryl ketone monomer present at no more
than about 5% by weight, and a random distribution of the diaryl
ketone in the copolymer, and an ultraviolet source to activate the
benzophenone to form crosslinks to create a covalently crosslinked
layer on a surface of the medical device.
17. The method of claim 16 wherein the layer has a friction
coefficient of no more than about 0.2.
18. The method of claim 16 wherein the copolymers, before the
photoinitiation, consist essentially of the polymerization product
of the N-vinyl pyrrolidinone and the diaryl ketone monomer.
19. The method of claim 16 wherein the medical device is selected
from the group consisting of a stent, a guidewire, a pacemaker
lead, a catheter, a nasogastric feeding tube, and an endotracheal
tube.
20. The method of claim 19 wherein the medical device is exposed to
the copolymers by a method chosen from the group consisting of
spraying, dipping, and painting.
21. The method of claim 20 wherein the copolymers are exposed to
the medical device in a solvent selected from the group consisting
of methanol, ethanol, 2-propanol, water, tetrahydrofuran, and
mixtures thereof, with the method further comprising evaporating
the solvent and drying the layer at a temperature ranging from
about 15 to about 80.degree. C.
22. A process of making a copolymer comprising preparing a solution
of N-vinyl pyrrolidinone in aqueous solution, adding a free radical
polymerization initiator dissolved in N-vinyl pyrrolidinone to the
solution, adding a aryl ketone vinyl monomer dissolved in N-vinyl
pyrrolidinone to the solution, and polymerizing the monomers to
form a random copolymer of the N-vinyl pyrrolidinone and the diaryl
ketone monomer.
23. The process of claim 22 wherein the aryl ketone comprises
benzophenone and the monomer comprises an acrylate group or a
methacrylate group.
24. The process of claim 22 wherein the aqueous solution solvent
consists essentially of water and/or alcohol.
Description
TECHNICAL FIELD OF THE INVENTION
[0001] The technical field, in general, relates to medical device
coatings and polymers for the same.
BACKGROUND
[0002] Medical devices may benefit from coatings that enhance
biocompatibility and other surface properties. The coatings provide
desirable surface properties without sacrificing the mechanical
properties of the underlying substrate.
SUMMARY
[0003] An embodiment of the invention is a copolymer of N-vinyl
pyrrolidinone and diaryl ketone monomers. The diaryl ketone
monomeric units are randomly dispersed through the length of the
copolymer. In contrast, a conventional method of synthesis places
the diaryl ketone mers in groups so that the copolymer is not
formed. These copolymers have been discovered to provide coatings
with desirable properties.
[0004] The copolymer of N-vinyl pyrrolidinone and diaryl ketone can
be made in a water soluble form, with an average molecular weight
of more than about 100,000, with at least about 60% by weight
N-vinyl pyrrolidinone, and with no more than about 5% by weight
diaryl ketone monomer. The water soluble nature of the copolymer
contributes to hydrophilicity of coatings made with the copolymer.
The molecular weight of more than about 100,000 provides
performance characteristics that are distinct from lower molecular
weight.
[0005] Another embodiment of the invention pertains to a coating
comprising copolymer of N-vinyl pyrrolidinone and diaryl ketone
monomers with the diaryl ketone monomeric units randomly dispersed
through the length of the copolymer.
[0006] Another embodiment of the invention pertains to a method of
making copolymer of N-vinyl pyrrolidinone and diaryl ketone
monomers where the diaryl ketone monomeric units are randomly
dispersed through the length of the copolymer. These copolymers
have been discovered to provide coatings with desirable
properties.
[0007] Another embodiment of the invention pertains to a method of
making a coating comprising copolymer of N-vinyl pyrrolidinone and
diaryl ketone monomers with the diaryl ketone monomeric units
randomly dispersed through the length of the copolymer.
[0008] The diaryl ketones in the copolymer are activated to make
covalent crosslinks to thereby form crosslinked layers. The water
soluble nature of the copolymer contributes to the hydrophilicity
of coatings made with the copolymer. The more than about 100,000
molecular weight of the copolymer provides significant control
distances between crosslinks.
BRIEF DESCRIPTION OF THE FIGURES
[0009] FIG. 1A depicts the structure of N-vinyl pyrrolidinone;
[0010] FIG. 1B depicts the structure of 4-benzoylphenyl
methacrylate; and
[0011] FIG. 1C depicts the polymerization of N-vinyl pyrrolidinone
and 4-benzoylphenyl methacrylate.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0012] A water soluble copolymer of N-vinyl pyrrolidinone (NVP) and
monomers with diaryl ketone monomeric units randomly dispersed
through the length of the copolymer is disclosed. The copolymer was
synthesized with approaches described herein. The water soluble
copolymer may be additionally crosslinked. In general, the
copolymer or the crosslinked copolymer may be used as lubricious
coatings on medical devices.
[0013] The term water soluble means that 1 L of water will dissolve
at least 1 g of the polymer. The term polymer refers to a molecule
composed of repeated subunits. The subunits are referred to as
mers. The terms monomeric unit or monomer unit are used
interchangeably with the term mer. The polymers may be formed by
polymerization of monomers. The monomers undergo chemical reactions
with each other to form covalent bonds. The monomers used may be
the same or different. The term copolymer refers to a polymer
derived from two or more monomeric units, as opposed to a
homopolymer where only one monomer is used. The term random means
that the probability of finding a given monomeric unit at any given
site in the chain is substantially independent of the nature of the
adjacent units. The term group indicates that the generically
recited chemical entity (e.g., alkyl group) may have any
substituent thereon which is consistent with the bond structure of
that group. For example, where the term `alkyl group` is used, that
term would not only include unsubstituted linear, branched and
cyclic alkyls, such as methyl, ethyl, isopropyl, tert-butyl,
cyclohexyl, dodecyl and the like, but also substituents having
heteroatom such as 3-ethoxylpropyl, 4-(N-ethylamino)butyl,
3-hydroxypentyl, 2-thiolhexyl, 1,2,3-tribromopropyl, and the like.
However, as is consistent with such nomenclature, no substitution
would be included within the term that would alter the fundamental
bond structure of the underlying group.
[0014] An example of an aryl ketone is benzophenone, which is a
diaryl ketone. FIG. 1A depicts the structure of NVP, FIG. 1B
depicts the structure of 4-benzoylphenyl methacrylate, and FIG. 1C
depicts the copolymer formed from the polymerization of these two
monomeric units. Diaryl ketone is a group that has a carbonyl group
in which the carbon of the carbonyl group is bound directly to two
carbon atoms that are part of aromatic rings. For example, the
simplest (monomeric)diaryl ketone is benzophenone, also called
diphenyl ketone. Other diaryl ketones are, for example,
acetophenone, anthraquinone, anthrone, and anthrone-like
heterocycles, and their substituted derivatives. Additional diaryl
ketones are 2-hydroxybenzophenone, 3-hydroxybenzophenone,
4-hydroxybenzophenone, 2,2'-dihydroxybenzophenone,
2,4-dihydroxybenzophenone, 3,4-dihydroxybenzophenone,
4,4'-dihydroxybenzophenone, 2,3,4-trihydroxybenzophenone,
2,4,4'-trihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone,
2-aminobenzophenone, 3-aminobenzophenone, 4-aminobenzophenone,
3,4-diaminobenzophenone, 4,4'-diaminobenzophenone,
4-(bromomethyl)benzophenone, 2-benzoylbenzoic acid,
3-benzoylbenzoic acid, 4-benzoylbenzoic acid, 4-benzoylbenzoyl
chloride, 4-isocyanatobenzophenone,
benzophenone-3,3',4,4'-tetracarboxylic dianhydride,
3-bromo-2',5-dichloro-2-hydroxybenzophenone,
2-hydroxy-2',3,5-trichlorobenzophenone,
3-bromo-5-chloro-2-hydroxybenzophenone,
5-bromo-2'-chloro-2-hydroxybenzophenone,
4'-chloro-5-fluoro-2-hydroxybenzophenone,
2',5-dichloro-2-hydroxybenzophenone, 5-bromo-2-hydroxybenzophenone,
4-fluoro-4'-hydroxybenzophenone, 2-amino-4'-bromobenzophenone,
2-amino-5-chlorobenzophenone, 4-amino-3-nitrobenzophenone,
2'-chloro-2-hydroxy-4-methylbenzophenone,
2'-chloro-2-hydroxy-5-methylbenzophenone,
2-hydroxy-5-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone,
2-amino-4-methylbenzophenone, benzoin, 4,4'-dimethoxybenzoin,
4-chlorobenzoin, benzyl 4-hydroxyphenyl ketone, benzyl
2,4-dihydroxyphenyl ketone,
2-phenyl-2',4',6'-trihydroxyacetophenone. The monomers may have an
aryl ketone group or other pendant groups.
[0015] The copolymer may consist essentially of the NVP and aryl
ketone monomeric units, or may further comprise additional
monomers. In this context, the term essentially refers to having at
least about 90% w/w of NVP in the copolymer, with the remaining 10%
being the aryl ketones or hydrophilic mers. Embodiments include a
water soluble copolymer with more than about 50% or about 60% w/w
of NVP monomeric units and no more than 5% or 10% aryl ketone
monomeric units; artisans will immediately appreciate that all the
ranges and values within the explicitly stated ranges are
contemplated. The copolymers may be prepared with less than 0.5%
aryl ketone monomeric units (e.g., benzophenone); artisans will
immediately appreciate that all the ranges and values within the
explicitly stated ranges are contemplated, e.g., about 0.2% or from
about 0.05% to about 0.25%.
[0016] In some embodiments the water soluble copolymer has no more
than about 5% w/w of an aryl ketone (or diaryl ketone) monomeric
unit; artisans will immediately appreciate that all the ranges and
values within the explicitly stated ranges are contemplated, e.g.,
from about 1% to about 5% or less than about 0.5%. The molecular
weight of the copolymer may be, for example, at least 100,000;
artisans will immediately appreciate that all the ranges and values
within the explicitly stated ranges are contemplated, e.g., from
about 100,000 to about 1,500,000, or about 900,000 to about
1,200,000. The rest of the copolymer may be NVP, or the NVP may be
present in a range of about 10% w/w to about 99% w/w, with other
mers set forth herein providing the balance, e.g., at least 60% NVP
monomeric units. Embodiments include coatings formed of such
copolymers.
[0017] Monomers for the copolymer may have active centers
comprising vinylic groups that form free radicals and undergo
polymerization. Examples of active centers are acrylate groups and
methacrylate groups. The monomers may have further substituents to
form derivatives of acrylate and methacrylate. Examples of such
substituents are hydroxyls and alkyls. Further monomers thus
include methyl methacrylate, ethyl methacrylate, n-alky
methacrylates, methyl ethyl acrylate, ethyl acrylate, n-alky
acrylates, and hydroxyethlymethacrylate.
[0018] The monomer groups may have further substituent groups.
Examples include poly(ethylene glycol) groups, poly(propylene
glycol) groups, poly(alkylene oxide) groups, silyl groups,
trimethoxysilyl groups, sulfonic acid groups, ammonium sulfatoethyl
groups, methylpropanesulfonic acid groups, polyhexanide groups, and
chlorhexidine groups. Further exemplary substituents include
sulfate groups, sulfabetaine groups, phopshorylcholine groups,
zwitterionic groups, 2-methacryloyloxyethyl phopshorylcholine
(MPC), carboxylic acids, heparin, heparin methacrylate, alcohols,
and hydroxyls. Further monomeric units are set forth in U.S. Pat.
Nos. 6,007,833, 6,849,669, 7,138,541, and 7,459,489, which are
hereby incorporated by reference herein for all purposes; in the
case of conflict, the present specification controls.
[0019] The term alkyl, unless otherwise specified, refers to a
saturated straight, branched, or cyclic hydrocarbon, and
specifically includes, e.g., methyl, ethyl, propyl, isopropyl,
butyl, isobutyl, t-butyl, pentyl, cyclopentyl, isopentyl,
neopentyl, hexyl, isohexyl, cyclohexyl, 3-methylpentyl,
2,2-dimethylbutyl, and 2,3-dimethylbutyl. The alkyl group can be
optionally substituted with any appropriate group, including but
not limited to one or more groups selected from halo, hydroxyl,
amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano,
sulfonic acid, sulfate, phosphonic acid, phosphate, or phosphonate,
either unprotected, or protected as necessary, as known to those
skilled in the art.
[0020] All of these various groups may be optionally derivatized
with substituent groups. Suitable substituent groups that may be
present on such a "substituted" group include e.g. halogens such as
fluoro, chloro, bromo and iodo; cyano; H, hydroxyl group; ester
group; ether group; a carbamate, an oxo acid group, an oxo carbon
group, an oxo carboxylic acid group, an oxo group, a ketone group;
nitro; azido; sulfhydryl; alkanoyl e.g. C.sub.1-6 alkanoyl group
such as acetyl and the like; carboxamido; alkyl groups, alkenyl and
alkynyl groups including groups having one or more unsaturated
linkages; alkoxy groups having one or more oxygen linkages; aryloxy
such as phenoxy; alkylthio groups; alkylsulfinyl groups;
alkylsulfonyl groups; aminoalkyl groups such as groups having one
or more N atoms; carbocyclic aryl; aryloxy such as phenoxy; aralkyl
having 1 to 3 separate or fused rings; aralkoxy having 1 to 3
separate or fused rings; or a heteroaromatic, heterocyclic, or
heteroalicyclic group having 1 to 4 separate or fused rings e.g.,
with one or more N, O or S atoms, e.g. coumarinyl, quinolinyl,
pyridyl, pyrazinyl, pyrimidyl, furyl, thienyl, thiazolyl, oxazolyl,
imidazolyl, indolyl, benzofuranyl, benzothiazolyl,
tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholino and
pyrrolidinyl. In some embodiments, the substituents may include
groups that include O, S, Se; N, P, Si, C and have between 2 and
about 150 atoms. In some embodiments, it is useful to limit the
size of any substituent to, e.g., less than about 150, less than
about 100, less than about 50, or less than about 20 atoms.
[0021] In some embodiments, suitable substituent groups include
these and other N-containing compounds e.g, amines, amides, amidium
ions, amine imides, amine oxides, aminium ions, aminonitrenes,
nitrenes, aminoxides, nitriles, and nitrile imides. Other suitable
substituent groups include these and other S-containing compounds,
e.g., sulfonic acid, sulfate, sulfonates, sulfamic acids, sulfanes,
sulfatides, sulfenamides, sulfenes, sulfenic acids, sulfenium ions,
sulfenyl groups, sulfenylium ions, sulfenyl nitrenes, sulfenyl
radicals, sulfides, sulfilimines, sulfimides, sulfimines,
sulfinamides, sulfinamidines, sulfines, sulfinic acids, sulfinic
anhydrides, sulfinimines, sulfinylamines, sulfolipids,
sulfonamides, sulfonamidines, sulfonediimines, sulfones, sulfonic
acids, sulfonic anhydrides, sulfonamides, sulfonium compounds,
sulfonphthaleins, sulfonylamines, sulfoxides, sulfoximides,
sulfoximines, sulfur diimides, thiols, thioacetals, thioaldehydes,
thioaldehyde S-oxides, thioanhydrides, thiocarboxylic acids,
thiocyanates, thioethers, thiohemiacetals, thioketones, thioketone
S-oxides, thiolates, and thionylamines. In some embodiments,
suitable substituent groups include these and other O-containing
compounds, e.g., having the form ROH (alcohol), RCOOH (carboxylic
acids), RCHO (aldehydes), RR'C.dbd.O (ketones), ROR' (ethers), and
RCOOR' (esters), with the R denoting a bond or atomic element. In
some embodiments, suitable substituent groups include these and
other P-containing compounds, e.g., phosphanes, phosphanylidenes,
phosphatidic acids, phosphazenes, phosphine oxides, phosphines,
phosphinic acids, phosphinidenes, phosphinous acids,
phosphoglycerides, phospholipids, phosphonic acids,
phosphonitriles, phosphonium compounds, phosphonium ylides,
phosphono, phosphorous acids, phosphoramides, and phosphoranes.
Carbon is useful for making substituents and the number of carbons
in a heteroatomic structure may be, e.g., between 1 and n-1 when
between 2 and n atoms are used to form a substituent with, e.g., 0,
P, S, or N. In some embodiments, it is useful to limit the size of
these substituents to, e.g., less than about 150, less than about
100, less than about 50, or less than about 20 atoms.
[0022] A variety of substituents are contemplated so that some
potential combinations of claimed embodiments may be unstable or
impractical to make. A person of ordinary skill in the art can
select appropriate stable compounds within the disclosed genus of
compounds based on the disclosure herein. Therefore, substituents
generally are limited to those substituents that result in
appropriate valence for the particular substituted element without
forming a charged compound or a radical (except for titratable
charged groups, stable zwitterionic forms and triplet neutral
radicals with formal unpaired spins with full valencies), as can be
conventionally determined by a person of ordinary skill in the
art.
[0023] The copolymer is a copolymer comprised of N-vinyl
pyrrolidinone (NVP) and monomers with an aryl ketone pendant group,
with the aryl ketone monomeric units being randomly distributed in
the copolymer. Mixing and conventional polymerization of monomeric
NVP and monomeric aryl ketones is not effective to synthesize such
a copolymer. It was discovered, however, that such a copolymer
could be synthesized using approaches described herein. For
example, dissolving the polymerization initiator in the NVP monomer
was found to be helpful. in preparing the copolymer with randomly
distributed aryl ketone monomeric units. Additionally, it was found
to be helpful to dissolve the aryl ketone monomer in the NVP. But
these approaches, alone or combined, were not sufficient to prepare
the desired copolymer as indicted in Examples 2 and 4 below. The
desired copolymer can be made, however, by adding these solutions
in a controlled manner to a larger solution, with ongoing
polymerization as illustrated in Examples 3 and 5 below. The
copolymers thus formed were soluble in water and other aqueous
solution sometimes with molecular weights of about 1,000,000. The
copolymers could be made to provide coatings with unexpected and
surprisingly favourable properties, including: thin, lubricious,
and durable coatings.
[0024] More specifically, a 4-benzoylphenyl methacrylate (an aryl
ketone monomeric unit) was synthesized (Example 1) and mixed in a
solvent with NVP. An initiator was dissolved in NVP and added to
the mixture of monomeric units. The initiator started
polymerization but poly(4-benzoylphenyl methacrylate) polymer was
produced instead of NVP-co-aryl ketone copolymer (Example 2).
Accordingly, this approach did not work even when the initiator was
dissolved in the NVP.
[0025] In contrast, in Example 3, the initiator was dissolved in
NVP to form a first solution and the aryl ketone was dissolved in
NVP in a second solution. A third solution of NVP in water was
prepared, and heated. The first solution was added to the third to
form a mixture. The second solution was slowly added dropwise to
the mixture. A water soluble copolymer of
poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl methacrylate) was
formed. Further, a high molecular weight in excess of about
1,000,000 was achieved.
[0026] Similarly, Example 4 demonstrates how the formation of
poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-methoxypolyethylene glycol 550 methacrylate) was
not successful, even when the various components were dissolved in
NVP and mixed. In this case, the methoxypolyethylene glycol 550
methacrylate polymerized with itself instead of making a copolymer.
But poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-methoxypolyethylene glycol 550 methacrylate) was
successfully made (Example 5) when the processes similar to the
procedure described in Example 2 was adapted.
[0027] These approaches are generally suited to the formation of
copolymer of N-vinyl pyrrolidinone (NVP) and monomers with an aryl
ketone pendant group, as evidenced by numerous examples:
poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl methacrylate) in
Example 3; poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-methoxypolyethylene glycol 550 methacrylate) in
Example 5; poly[N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-(2-methacryloyloxy)ethyl
dimethyl-(3-sulfopropyl)ammonium hydroxide] in Example 6;
poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-(3-methacryloylamino)prop
dimethyl-(3-sulfopropyl)ammonium hydroxide] in Example 7;
poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-2-methacryoyloxyethyl phosphorylcholine) in Example
8; poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-ammonium sulfatoethyl methacrylate) in Example 9;
poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-acrylic acid) in Example 10;
poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-dimethylaminoethyl methacrylate) in Example 11;
poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-2-hydroxyethyl methacrylate) in Example 12 and
poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-polyhexanide methacrylate) in Example 13. These
copolymers and derivatives thereof that further comprise additional
groups or substitutions are embodiments of inventions, as are
coatings of the same. Azobisisobutyronitrile (AIBN) is an initiator
for polymerization of the copolymer; others are also suitable, as
is known to artisans.
[0028] Another embodiment of the invention is a coating or a layer
comprising a copolymer as set forth herein, for instance, a
copolymer of N-vinyl pyrrolidinone (NVP) and monomers with an aryl
ketone pendant group. Such copolymers can form lubricious and tough
coatings. Example 3 describes synthesis of such a copolymer.
Polymers made from the same precursors, however, did not provide
these characteristics; the properties of a coating of the polymer
of Example 2 were observed to be quite poor compared to the
copolymer of Example 3 (see Examples 14 and 15).
[0029] Moreover, the copolymer coatings had excellent flexibility
and were highly lubricious. The friction coefficient can be defined
as the force required to move a sample through a clamp of constant
force divided by the force that is applied by the clamp. For
example, if the force required to pull a sample through a clamp,
which has a force of 400 g applied to it, is 100 g, then the
friction coefficient will be 0.25. Friction coefficients for
coatings of the copolymers range from 0.5 to 0.005 depending on the
substrate used. The coating reduces the friction coefficient by
about 50 to about 99.5% compared with the uncoated sample; artisans
will immediately appreciate that all the ranges and values within
the explicitly stated ranges are contemplated, e.g, a reduction of
about 60%, about 90%, or from about 80% to about 99.5%.
[0030] Embodiments include a coating comprising covalently
crosslinked copolymers as set forth herein, the coating being
hydrophilic, highly flexible, and durable. Highly flexible means
that a coating of about 50 to about 200 .mu.m thickness applied to
a substrate will not crack as observed by the naked eye. The
contact angle is the angle at which a liquid/vapor interface meets
a solid surface, with lower contact angles representing a more
hydrophilic (wettable) surface. Typical contact angles for water on
surfaces coated with the present invention are between about
0.degree. and about 30.degree.; artisans will immediately
appreciate that all the ranges and values within the explicitly
stated ranges are contemplated, e.g, from about 0.1 to about
20.degree.. Durability may be assessed by dying a coated substrate
and then subjecting the coated article to a wet abrasion test. For
example, by rubbing the wet coated article between the index finger
and thumb using firm pressure for at least 20 cycles. If the dye
does not fade, or the coating re-dyes to a similar intensity, then
the coating passes the durability assessment. If the dye fades and
does not re-dye, then the coating has not linked sufficiently and
will delaminate from the substrate (as in Example 14).
[0031] A coating material is formed on a substrate. A substrate
generally presents a surface onto which the coating material can be
deposited, and the substrate may comprise a plurality of layers in
which the surface relates to an upper most layer. The substrate
surface can be treated to prepare the surface for adhesion of the
coating material. Prior to preparation of the surface, the surface
can be cleaned and/or smoothed as appropriate. Suitable substrate
surfaces can comprise any reasonable material. Some substrates of
particular interest include, for example, stainless steel, metals,
nitinol, engineering polymers, polyethylene, polypropylene,
polytetrafluoroethylene, polyurethane, polyamide, polyether block
amide, inorganic materials, polymer substrates, such as organic
polymers, composites thereof and combinations thereof across a
surface and/or in layers of the substrate. The substrate may be a
surface of a medical device, e.g., a surface exposed to blood
and/or for temporary or permanent use inside a body. Examples of
such medical devices are a stent, a guidewire, a pacemaker lead, a
catheter, a medical balloon, a nasogastric feeding tube, a PICC
line, and an endotracheal tube. Catheters may be, for example, a
urinary catheter, an infusion catheter, and a drainage catheter.
The term medical device as used herein is broad and includes
medical diagnostic devices, for example, surfaces exposed to a
biological sample for a diagnostic purpose.
[0032] In general, any suitable coating process can be used to
deliver the copolymer to a substrate. Suitable coating approaches
can include, for example, spin coating, spray coating, dip coating,
painting, and casting. The aryl ketones may be activated after the
copolymer is present on the substrate to promote crosslinking of
the copolymers with each other to form a covalently crosslinked
matrix. Light-based activation may be used, or other suitable
means, e.g., heat. The coating material can be applied in multiple
coating steps to provide greater control over the coating process.
For example, multiple spin coatings can be performed to yield an
ultimate coating thickness desired. The heat processing described
below can be applied after each coating step or after a plurality
of coating steps. Solvents for the copolymers in the coating
process may be aqueous or alcoholic or a mixture thereof. Examples
of alcohol include methanol, ethanol, and 2-propanol. Further
solvents are water, dimethylsulfoxide, tetrahydrofuran, and
dichloromethane. The method may comprise evaporating the solvent
and drying the layer at a temperature ranging from about 15 to
about 80.degree. C.; artisans will immediately appreciate that all
the ranges and values within the explicitly stated ranges are
contemplated. The solvent may be aqueous, a term that means a
solvent that is at least 10% v/v water, with the balance of the
solvent being liquids miscible with the water. The solvent may
consist essentially of water and/or alcohol, with the term
essentially, in this context, meaning that the liquid phase of the
solvent is at least 90% v/v water or alcohol and the balance of the
liquid phase does not substantially interfere with the coating
process.
[0033] The thickness of the coating generally can be a function of
the coating process that is chosen. In some embodiments, the
coating materials can have an average thickness of between about 1
.mu.m and about 1 mm; artisans will immediately appreciate that all
the ranges and values within the explicitly stated ranges are
contemplated, e.g., about 10 .mu.m to about 200 .mu.m, or about 5
to about 20 .mu.m.
[0034] Copolymers of N-vinyl pyrrolidinone (NVP) and monomers with
an aryl ketone pendant group were made into effective coatings on a
variety of substrates, including polyurethane (Examples 15 and 16),
polyether block polymers (Example 17), polyamide (Example 18), and
stainless steel (Example 19). The coatings were excellent and were
flexible, durable, lubricious, and hydrophilic.
EXAMPLES
Example 1
Synthesis of 4-benzoylphenyl methacrylate
[0035] To a 100 mL round-bottomed flask equipped with a magnetic
stirrer bar and an addition funnel was added 4-hydroxybenzophenone
(1 g, 5.04 mmol) and CH.sub.2Cl.sub.2 (35 mL). The mixture was
cooled to 0.degree. C. and methacryloyl chloride (0.39 mL, 4.04
mmol) was added in one portion. After 30 minutes, triethylamine
(0.7 mL, 5.04 mmol) dissolved in CH.sub.2Cl.sub.2 (10 mL) was added
dropwise over 30 minutes. The reaction mixture was allowed to stir
for a further 1 hour at 0.degree. C. and then at room temperature
for 3 hours. After this time, the organic mixture was washed with
0.1% NaOH (3.times.100 mL) and water (5.times.100 mL). The combined
organic layers were dried over MgSO.sub.4 and then concentrated in
vacuo to afford a crude product. The crude product was purified by
column chromatography (100% CH.sub.2Cl.sub.2) to provide the
compound as a white solid (yield=75%, 1 g).
Example 2
Failed Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate)
[0036] This Example demonstrates that merely combining a mixture of
precursors does not provide for synthesis of
poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl methacrylate).
Instead, it results in a varied a mixture of polymers, apparently
as a result of varied precursor reactivity ratios. In this case,
poly(4-benzoylphenyl methacrylate) is apparently produced as
evidenced by the resultant precipitates.
[0037] To a 250 mL conical flask equipped with a magnetic stirrer
bar was added N-vinyl-2-pyrrolidinone (NVP) (30 g), 4-benzoylphenyl
methacrylate (0.1 g) and deionized water (70 mL). The mixture was
purged with N.sub.2 for 20 minutes whilst being heated to
70.degree. C. After this time, azobisisobutyronitrile (AIBN) (0.1 g
dissolved in NVP, 2 mL) was added in one portion to initiate
polymerization. After approximately 5 minutes the solution became
cloudy and insoluble precipitates formed as a result of
poly(4-benzoylphenyl methacrylate) precipitating out of
solution.
Example 3
Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate)
[0038] To a 250 mL conical flask equipped with a magnetic stirrer
bar was added NVP (30 g) and deionized water (70 mL). The mixture
was purged with N.sub.2 for 20 minutes whilst being heated to
70.degree. C. After this time, AIBN (0.1 g dissolved in NVP, 2 mL)
was added in one portion. About 8 minute after the addition of
AIBN, 4-benzoylphenyl methacrylate (0.1 g dissolved in NVP, 2 mL)
was added dropwise over a period of 10 minutes. Polymerization was
carried out for 1 hour, after which time the viscous mixture was
allowed to cool to room temperature and then dissolved in water
(150 mL). The resultant polymer solution was clear, with no
evidence of poly(-benzoylphenyl methacrylate) precipitation. The
polymer solution was dialyzed against water (10 L) for 16 h and
then freeze dried to afford the title polymer as a white solid
(yield=32 g). Gel permeation chromatography (GPC) was carried out
on the white solid using a Perkin-Elmer Series 200 GPC system
equipped with PL-AQUAGEL-OH 40 and PL-AQUAGEL-OH 50 columns
(300.times.7.5 mm), a PL-AQUAGEL 5 .mu.m guard column and a
refractive index (RI) detector. Molecular weights were determined
relative to narrow poly(ethylene oxide)/poly(ethylene glycol)
standards (Varian, Inc) using a mobile phase consisting of 0.02%
NaN.sub.3 in water at a flow rate of 1.0 mL/min at 30.degree. C.
with a sample injection of 50 .mu.L. Typically, molecular weights
in the 1,000,000 gmol.sup.-1 range were measured.
Example 4
Failed Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-methoxypolyethylene glycol 550 methacrylate)
[0039] To a 250 mL conical flask equipped with a magnetic stirrer
bar was added NVP (27 g), methoxypolyethylene glycol 550
methacrylate (MPEG 550 methacrylate) (6 g) and deionised water (100
mL). The mixture was purged with N.sub.2 for 20 minutes whilst
being heated to 70.degree. C. After this time, AIBN (0.1 g
dissolved in NVP, 2 mL) was added in one portion to initiate
Polymerization. The solution became viscous within 5 minutes and a
gel had formed within 8 minutes so that 4-benzoylphenyl
methacrylate could not be added. The reaction was terminated by the
addition of deionised water (150 mL). The gelled polymer was
dialyzed against water (10 L) for 16 h and then freeze dried to
afford 5 g of product. The polymeric product was insoluble in
water, ethanol, dimethyl sulfoxide, dimethylformamide and mixtures
thereof, indicating that a cross-linked product had been afforded.
Evidently, the MPEG 550 methacrylate had homo-polymerized and, as a
result of residual cross-linker present in the monomer, had formed
an insoluble cross-linked gel.
[0040] The polymer was characterised by infrared spectroscopy using
a Perkin-Elmer Paragon 1000 FT-IR spectrometer. Samples were
recorded as a thin film. The absence of a C.dbd.O (amide)
absorption at around 1650 cm.sup.-1 indicated that no NVP had been
incorporated into the polymer.
Example 5
Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-methoxypolyethylene glycol 550 methacrylate)
[0041] To a 250 mL conical flask equipped with a magnetic stirrer
bar was added NVP (27 g) and deionised water (100 mL). The mixture
was purged with N.sub.2 for 20 minutes whilst being heated to
70.degree. C. After this time, AIBN (0.1 g dissolved in NVP, 2 mL)
was added in one portion. About 8 minutes after the addition of
AIBN, 4-benzoylphenyl methacrylate (0.1 g dissolved in NVP, 2 mL)
was added dropwise over a period of 10 minutes. Careful control
over the rate and time of MPEG 550 methacrylate addition ensured
the monomer did not homo-polymerize and did not cross-link to form
a gel. Then, MPEG 550 methacrylate (6 g) containing 4-benzoylphenyl
methacrylate (0.03 g) (dissolved in NVP, 1 mL) was added dropwise
over a period of 10 minutes. Polymerization was carried out for 1
hour, whilst maintaining the reaction temperature between
70-75.degree. C. After this time, the reaction was terminated by
the addition of water (150 mL). The polymer solution was dialyzed
against water (10 L) for 16 h and then freeze dried to afford the
title polymer as a white solid (yield=30 g).
[0042] FT-IR analysis of the white solid revealed the presence of a
strong absorption at around 1650 cm.sup.-1, which was attributed to
the C.dbd.O (amide) of the polymeric NVP. An absorption at around
1100 cm.sup.-1 provided evidence for the presence of the
polyethylene glycol unit (C--O--C).
Example 6
Synthesis of poly[N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-(2-methacryloyloxy)ethyl
dimethyl-(3-sulfopropyl)ammonium hydroxide]
[0043]
Monomer2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium
hydroxide (MEDSAH) was polymerised with NVP and 4-benzoylphenyl
methacrylate following the procedure as described in Example 5
except that MEDSAH (6 g) was dissolved in water (10 mL) containing
4-benzoylphenyl methacrylate (0.03 g) (dissolved in NVP, 1 mL). The
yield of the title polymer was 29 g.
[0044] FT-IR analysis revealed the presence of a strong absorption
at around 1650 cm.sup.-1, which was attributed to the C.dbd.O
(amide) of the polymeric NVP and absorptions due to S.dbd.O at
around 1200 cm.sup.-1 and 1000 cm.sup.-1 from the MEDSAH.
Example 7
Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-(3-methacryloylamino)propyl
dimethyl-(3-sulfopropyl)ammonium hydroxide]
[0045]
Monomer3-(Methacryloylamino)propyl]dimethyl-(3-sulfopropyl)ammonium
hydroxide (MPDSAH) was polymerised with NVP and 4-benzoylphenyl
methacrylate following the procedure as described in Example 6. The
yield of the title polymer was 29 g.
[0046] FT-IR analysis revealed the presence of a strong absorption
at around 1650 cm.sup.-1, which was attributed to the C.dbd.O
(amide) of the polymeric NVP and absorptions due to S.dbd.O at
around 1200 cm.sup.-1 and 1000 cm.sup.-1 from the MPDSAH.
Example 8
Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-2-methacryoyloxyethyl phosphorylcholine)
[0047] Monomer 2-Methacryloyloxyethyl phopshorylcholine (MPC) was
polymerised with NVP and 4-benzoylphenyl methacrylate following the
procedure as described in Example 6. The yield of the title polymer
was 25 g.
[0048] FT-IR analysis revealed absorptions at around 950, 1080 and
1260 cm.sup.-1, which were attributed to the phosphate group of MPC
and a strong absorption at around 1650 cm.sup.1, which was
attributed to the C.dbd.O (amide) of the polymeric NVP.
Example 9
Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-ammonium sulfatoethyl methacrylate)
[0049] Ammonium sulfatoethyl methacrylate (SEM) was polymerised
with NVP and 4-benzoylphenyl methacrylate following the procedure
as described in Example 6. The yield of the title polymer was 28
g.
Example 10
Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-acrylic acid)
[0050] Acrylic acid (sodium salt) was polymerised with NVP and
4-benzoylphenyl methacrylate following the procedure as described
in Example 6. Once polymerised, the pH was reduced to .about.3 to
form the free acid. The yield of the title polymer was 26 g.
Example 11
Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-dimethylaminoethyl methacrylate)
[0051] Dimethylaminoethyl methacrylate was polymerised with NVP and
4-benzoylphenyl methacrylate following the procedure as described
in Example 5. The yield of the title polymer was 29 g.
Example 12
Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-2-hydroxyethyl methacrylate)
[0052] 2-hydroxyethyl methacrylate (HEMA) was polymerised with NVP
and 4-benzoylphenyl methacrylate following the procedure as
described in Example 5 The yield of the title polymer was 30 g.
Example 13
Synthesis of poly(N-vinyl-2-pyrrolidinone-co-4-benzoylphenyl
methacrylate-co-polyhexanide methacrylate)
[0053] Polyhexanide methacrylate was polymerised with NVP and
4-benzoylphenyl methacrylate following the procedure as described
in Example 6. The yield of the title polymer was 23 g.
Example 14
Coating of poly(urethane) tube with polymer from Example 2
[0054] The polymer prepared in Example 2 was dissolved in a mixture
of isopropyl alcohol (IPA)/water to give a final polymer
concentration of 3% w/v. A clean poly(urethane) tube was then
immersed into the coating solution and left for approximately 30
seconds. After this time, the tube was slowly withdrawn from the
solution and allowed to dry at room temperature for at least 10
minutes. Once dry, the coated poly(urethane) tube was exposed to a
UVASPOT 1000 F UV lamp for 3 minutes. Upon exposure to water, the
coating was easily delaminated from the surface indicating that no
chemical cross-linking had occurred.
Example 15
Coating of poly(urethane) tube with co-polymer from Example 3
[0055] The co-polymer prepared in Example 3 was dissolved in a
mixture of IPA/water to give a final polymer concentration of 3%
w/v. A clean poly(urethane) tube was then immersed into the coating
solution and left for approximately 30 seconds. After this time,
the tube was slowly withdrawn from the solution and allowed to dry
at room temperature for at least 10 minutes. Once dry, the coated
poly(urethane) tube was exposed to a UVASPOT 1000 F UV lamp for 3
minutes to afford a thin, durable, cross-linked coating, which upon
exposure to water became highly lubricious.
Example 16
Coating of poly(urethane) tube with co-polymer from Example 5
[0056] The co-polymer prepared in Example 5 was dissolved in a
mixture of IPA/water to give a final polymer concentration of 3%
w/v. A clean poly(urethane) tube was then immersed into the coating
solution and left for approximately 30 seconds. After this time,
the tube was slowly withdrawn from the solution and allowed to dry
at room temperature for at least 10 minutes. Once dry, the coated
poly(urethane) tube was exposed to a UVASPOT 1000 F UV lamp for 3
minutes to afford a thin, durable, cross-linked coating, which upon
exposure to water became highly lubricious. The coating also
exhibited excellent flexibility.
Example 17
Coating of PEBAX tube with co-polymer from Example 5
[0057] The co-polymer prepared in Example 5 was dissolved in a
mixture of IPA/water to give a final polymer concentration of 3%
w/v. A clean PEBAX tube was then immersed into the coating solution
and left for approximately 30 seconds. After this time, the tube
was slowly withdrawn from the solution and allowed to dry at room
temperature for at least 10 minutes. Once dry, the coated PEBAX
tube was exposed to a UVASPOT 1000 F UV lamp for 3 minutes to
afford a thin, durable, cross-linked coating, which upon exposure
to water became highly lubricious. The coating also exhibited
excellent flexibility. PEBAX is a trade name for a block copolymer
obtained by polycondensation of a carboxylic acid polyamide (PA6,
PA11, PA12) with an alcohol termination polyether (PTMG, PEG).
Example 18
Coating of poly(amide) tube with co-polymer from Example 5
[0058] The co-polymer prepared in Example 5 was dissolved in a
mixture of IPA/water to give a final polymer concentration of 3%
w/v. A clean poly(amide) tube was then immersed into the coating
solution and left for approximately 30 seconds. After this time,
the tube was slowly withdrawn from the solution and allowed to dry
at room temperature for at least 10 minutes. Once dry, the coated
poly(amide) tube was exposed to a UVASPOT 1000 F UV lamp for 3
minutes to afford a thin, durable, cross-linked coating, which upon
exposure to water became highly lubricious. The coating also
exhibited excellent flexibility.
Example 19
Coating of stainless steel guidewire with co-polymer from Example
5
[0059] A commercially available polyester, such as DYNAPOL.RTM.
L490, was first dissolved in THF at a concentration of 3% w/v. A
clean stainless steel guidewire was then immersed into the solution
and left for approximately 30 seconds. After this time, the
guidewire was slowly withdrawn from the solution and dried in an
oven at 60.degree. C. for 30 minutes to afford a polyester coated
guidewire.
[0060] The co-polymer prepared in Example 5 was dissolved in a
mixture of IPA/water to give a final polymer concentration of 3%
w/v. The polyester coated guidewire was then immersed into the
coating solution and left for approximately 30 seconds. After this
time, the tube was slowly withdrawn from the solution and allowed
to dry at room temperature for at least 10 minutes. Once dry, the
coated guidewire was exposed to a UVASPOT 1000 F UV lamp for 3
minutes to afford a thin, durable, cross-linked coating, which upon
exposure to water became highly lubricious. The coating also
exhibited excellent flexibility.
Further Disclosure
[0061] The embodiments above are intended to be illustrative and
not limiting. Additional embodiments are within the claims. In
addition, although the present invention has been described with
reference to particular embodiments, those skilled in the art will
recognize that changes can be made in form and detail without
departing from the spirit and scope of the invention. Any
incorporation by reference of documents above is limited such that
no subject matter is incorporated that is contrary to the explicit
disclosure herein.
[0062] A coating on a medical device comprising hydrophilic layer
comprising copolymers covalently crosslinked by photoinitiation of
diaryl ketones pendant on the copolymers, with the copolymers,
before photoinitiation, being polymerized from a plurality of
monomers comprising N-vinyl pyrrolidinone and diaryl ketone vinyl
monomer, having a weight average molecular weight of more than
about 100,000, at least about 60% by weight N-vinyl pyrrolidinone,
no more than about 5% by weight of diaryl ketone monomer that
provides the pendant diaryl ketones, and a random distribution of
the diaryl ketones.
[0063] An isolated set of polymers comprising copolymers
polymerized from monomers comprising N-vinyl pyrrolidinone monomer
and a diaryl ketone vinyl monomer, with the copolymers having a
weight average molecular weight of more than about 100,000, at
least about 60% by weight N-vinyl pyrrolidinone, no more than about
5% by weight diaryl ketone monomer, and a random distribution of
the diaryl ketone in the copolymer.
[0064] A method of coating a medical device comprising exposing a
medical device to copolymers having a weight average molecular
weight of more than about 100,000, at least about 60% by weight
N-vinyl pyrrolidinone, diaryl ketone monomer present at no more
than about 5% by weight, and a random distribution of the diaryl
ketone in the copolymer, and an ultraviolet source to activate the
benzophenone to form crosslinks to create a covalently crosslinked
layer on a surface of the medical device.
[0065] A process of making a copolymer comprising preparing a
solution of N-vinyl pyrrolidinone in aqueous solution, adding a
free radical polymerization initiator dissolved in N-vinyl
pyrrolidinone to the solution, adding a aryl ketone vinyl monomer
dissolved in N-vinyl pyrrolidinone to the solution, and
polymerizing the monomers to form a random copolymer of the N-vinyl
pyrrolidinone and the diaryl ketone monomer.
[0066] A copolymer comprising hydrophilic monomeric units and an
aryl and/or diaryl ketone monomeric units, and a polyethylene
backbone, wherein the copolymers have a weight average molecular
weight of more than about 100,000, at least about 60% by weight of
the hydrophilic monomeric units, no more than about 5% by weight
diaryl ketone monomeric units, and a random distribution of the
diaryl ketone monomeric units along the polyethylene backbone of
the copolymer.
[0067] A process of making a copolymer comprising preparing a
solution of a hydrophilic monomer in aqueous solution, adding a
free radical polymerization initiator dissolved in the hydrophilic
monomer to the solution, adding a diaryl ketone monomer dissolved
in the hydrophilic monomer to the solution, and polymerizing the
monomers to form a random copolymer of the hydrophilic monomer and
the diaryl ketone monomer.
[0068] A hydrophilic coating on a medical device comprising
polyethylene copolymers covalently crosslinked by diaryl ketones
pendant on the copolymers, wherein the copolymer comprises
hydrophilic monomeric units and diaryl ketone vinyl monomeric
units, having an average molecular weight of more than about
100,000, at least about 60% by weight of the hydrophilic monomeric
units, no more than about 5% by weight of diaryl ketone monomeric
units that provides the pendant diaryl ketones, and a random
distribution of the diaryl ketones along the polyethylene
backbone.
[0069] A method of coating a medical device comprising exposing a
medical device to copolymers having a weight average molecular
weight of more than about 100,000, at least about 60% by weight
N-vinyl pyrrolidinone, diaryl ketone monomer present at no more
than about 5% by weight, and a random distribution of the diaryl
ketone in the copolymer, and activating the diaryl ketone in the
copolymer to form crosslinks to create a covalently crosslinked
layer on a surface of the medical device.
[0070] A medical device comprising a copolymer or a coating as set
forth herein, which medical device may include a medical device as
set forth herein. A method, copolymer, coating, or process wherein
(i) a coating of the copolymer has a friction coefficient of no
more than about 0.2 or reduces a friction coefficient by more than
about 50%; artisans will immediately appreciate that all the ranges
and values within the explicitly stated ranges are contemplated
and/or (ii) wherein the diaryl ketone is benzophenone and/or (iii)
wherein the diaryl ketone monomer comprises a methacrylate group or
an acrylate group and/or (iv) wherein the diaryl ketone of the
copolymers is selected from the group consisting of
2-hydroxybenzophenone, 3-hydroxybenzophenone,
4-hydroxybenzophenone, 2,2'-dihydroxybenzophenone,
2,4-dihydroxybenzophenone, 3,4-dihydroxybenzophenone,
4,4'-dihydroxybenzophenone, 2,3,4-trihydroxybenzophenone,
2,4,4'-trihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone,
2-aminobenzophenone, 3-aminobenzophenone, 4-aminobenzophenone,
3,4-diaminobenzophenone, 4,4'-diamonibenzophenone,
4-(bromomethyl)benzophenone, 2-benzoylbenzoic acid,
3-benzoylbenzoic acid, 4-benzoylbenzoic acid, 4-benzoylbenzoyl
chloride, 4-isocyanatobenzophenone,
benzophenone-3,3',4,4'-tetracarboxylic dianhydride,
3-bromo-2',5-dichloro-2-hydroxybenzophenone,
2-hydroxy-2',3,5-trichlorobenzophenone,
3-bromo-5-chloro-2-hydroxybenzophenone,
5-bromo-2'-chloro-2-hydroxybenzophenone,
4'-chloro-5-fluoro-2-hydroxybenzophenone,
2',5-dichloro-2-hydroxbenzophenone, 5-bromo-2-hydroxybenzophenone,
4-fluoro-4'-hydroxybenzophenone, 2-amino-4'-bromobenzophenone,
2-amino-5-chlorobenzophenone, 4-amino-3-nitrobenzophenone,
2'-chloro-2-hydroxy-4-methylbenzophenone,
2'-chloro-2-hydroxy-5-methylbenzophenone,
2-hydroxy-5-methylbenzophenone, 2-hydroxy-4-methoxybenzophenone,
2-amino-4-methylbenzophenone, benzoin, 4,4'-dimethoxybenzoin,
4-chlorobenzoin, benzyl 4-hydroxyphenyl ketone, benzyl
2,4-dihydroxyphenyl ketone,
2-phenyl-2',4',6'-trihydroxyacetophenone and/or (v) wherein the
diaryl ketone monomer comprises a polymerizable group selected from
the group consisting of acrylate groups, methacrylate groups, and
methylmethacrylate groups and/or (vi) wherein the plurality of
monomers further comprises one or more monomers selected from the
group consisting of poly(ethylene glycol) methacrylate,
polypropylene glycol) methacrylate, poly(ethylene glycol) methyl
ether methacrylate, poly(ethylene glycol) ethyl ether methacrylate,
3-trimethoxysilyl propyl methacrylate, vinyl sulfonic acid (sodium
salt), ammonium sulfatoethyl methacrylate,
2-acryloylamido-2-methylpropanesulfonic acid monomer,
[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium
hydroxide (MEDSAH),
[3-(methacryloamino)propyl]dimethyl-(3-sulfopropyl)ammonium
hydroxide (MPDSAH), 2-methacryloyloxyethyl phopshorylcholine (MPC),
acrylic acid (sodium salt), dimethylaminoethyl methacrylate,
2-hydroxyethyl methacrylate (HEMA), polyhexanide methacrylate and
chlorhexidine methacrylate and/or (vii) wherein the plurality of
monomers further comprises a monomer that comprises a polyethylene
glycol pendant group and/or (viii) wherein the plurality of
monomers further comprises a monomer that comprises a pendant group
terminating in a sulfonate group and/or (ix) wherein the plurality
of monomers further comprises a monomer that comprises a silyl
pendant group and/or (x) 1 wherein the plurality of monomers
further comprise a monomer that comprises a zwitterionic group
and/or (xi) wherein the plurality of monomers further comprise a
monomer that comprises a hydroxyl group and/or (xii) wherein the
copolymers, before photoinitiation, consist essentially of the
polymerization product of the N-vinyl pyrrolidinone and the diaryl
ketone monomer.
* * * * *